rs35495464

Positions:

• chr2-230172900-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_080424.4(SP110):​c.1650T>C​(p.Gly550=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 1,613,902 control chromosomes in the GnomAD database, including 4,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (302 hom., cov: 32)
  • Exomes 𝑓: 0.069 (3957 hom.)
• Consequence: SP110 NM_080424.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.640

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-230172900-A-G is Benign according to our data. Variant chr2-230172900-A-G is described in ClinVar as [Benign]. Clinvar id is 334900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4	c.1650T>C	p.Gly550=	synonymous_variant	15/19	ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11	c.1650T>C	p.Gly550=	synonymous_variant	15/19	2	NM_080424.4	P1
	ENST00000628587.2	n.1098+707A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8079 AN: 152144 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.0630

GnomAD3 exomes AF: 0.0599 AC: 15054 AN: 251396 Hom.: 591 AF XY: 0.0619 AC XY: 8415 AN XY: 135860

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.0357

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.00332

Gnomad SAS exome AF: 0.0540

Gnomad FIN exome AF: 0.0316

Gnomad NFE exome AF: 0.0817

Gnomad OTH exome AF: 0.0738

GnomAD4 exome AF: 0.0693 AC: 101303 AN: 1461640 Hom.: 3957 Cov.: 31 AF XY: 0.0694 AC XY: 50456 AN XY: 727142

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.0383

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.00171

Gnomad4 SAS exome AF: 0.0526

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0759

Gnomad4 OTH exome AF: 0.0673

GnomAD4 genome AF: 0.0530 AC: 8072 AN: 152262 Hom.: 302 Cov.: 32 AF XY: 0.0507 AC XY: 3772 AN XY: 74440

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0518

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0535

Gnomad4 FIN AF: 0.0337

Gnomad4 NFE AF: 0.0798

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0753 Hom.: 242

Bravo AF: 0.0521

Asia WGS AF: 0.0280 AC: 97 AN: 3478

EpiCase AF: 0.0807

EpiControl AF: 0.0834

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35495464; hg19: chr2-231037616;